A critical role for miR-184 in the fate determination of oligodendrocytes

Afrang, Negin and Tavakoli, Rezvan and Tasharrofi, Nooshin and Alian, Amir and Sohi, Alireza Naderi and Kabiri, Mahboubeh and Fathi-Roudsari, Mehrnoosh and Soufizomorrod, Mina and Rajaei, Farzad and Soleimani, Masoud and Kouhkan, Fatemeh (2019) A critical role for miR-184 in the fate determination of oligodendrocytes. STEM CELL RESEARCH & THERAPY, 10.

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Abstract

BackgroundNew insights on cellular and molecular aspects of both oligodendrocyte (OL) differentiation and myelin synthesis pathways are potential avenues for developing a cell-based therapy for demyelinating disorders comprising multiple sclerosis. MicroRNAs (miRNA) have broad implications in all aspects of cell biology including OL differentiation. MiR-184 has been identified as one of the most highly enriched miRNAs in oligodendrocyte progenitor cells (OPCs). However, the exact molecular mechanism of miR-184 in OL differentiation is yet to be elucidated.Methods and resultsBased on immunochemistry assays, qRT-PCR, and western blotting findings, we hypothesized that overexpression of miR-184 in either neural progenitor cells (NPCs) or embryonic mouse cortex stimulated the differentiation of OL lineage efficiently through regulating crucial developmental genes. Luciferase assays demonstrated that miR-184 directly represses positive regulators of neural and astrocyte differentiation, i.e., SOX1 and BCL2L1, respectively, including the negative regulator of myelination, LINGO1. Moreover, blocking the function of miR-184 reduced the number of committed cells to an OL lineage.ConclusionsOur data highlighted that miR-184 could promote OL differentiation even in the absence of exogenous growth factors and propose a novel strategy to improve the efficacy of OL differentiation, with potential applications in cell therapy for neurodegenerative diseases.

Item Type: Article
Subjects: R Medicine > RZ Other systems of medicine
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: sobhan rezaiian
Date Deposited: 23 Apr 2019 08:50
Last Modified: 23 Apr 2019 08:50
URI: http://eprints.lums.ac.ir/id/eprint/1655

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